Numerous macrocyclic peptides and depsipeptides have been isolated from natural sources which complex sodium, potassium and calcium ions to varying degrees and effect transmembrane transport of these species. Cation transport is important to many biological processes and divalent calcium is the physiologic regulator of muscle contraction. In order to better understand the role ionophores play in transport and in the hope of making simple, synthetic ionophores which are cation selective and physiologically active, we propose to prepare a new group of crown ethers based on the "lariat ether" concept we have recently developed. These compounds will have 15- or 18-membered macrocyclic polyether (crown ether) or monoazapolyether rings capable of selective cation binding. To these will be appended peptide and depsipeptide side-chains whose structures are suggested by fragments of naturally occurring ionophores. The amide and ester donor groups in these residues should serve as secondary donor groups for the ring-bound cation. Such compounds will allow study, modelling and tailoring of ionophore features while remining synthetically accessible.